African trypanosomiasis is a protozoan disease of medical and economic importance in which species of Trypanosoma cause fatal sleeping sickness in man. Trypanosomes are able to evade immunological destruction in the host by rearrangement of genes encoding the variant surface glycoprotein (VSG) molecule comprising the trypanosome surface coat. Biological variation also is detectable in African trypanosomes independent of antigenic variation associated with VSG gene expression. The phenotypic nature and genetic bases of this biological variation, which occurs within clonally derived trypanosome populations, will be determined. The model system to be employed is one in which two different clones of Trypanosoma brucei rhodesiense express the same surface coat and VSG gene, but differ markedly in other biological traits such as virulence. These two trypanosome populations will be studied at the molecular level by analysis of differentially expressed genes. Such virulence-associated gene expression may be the basis of the clinically broad spectrum of the disease caused by trypanosomes. Contemporary methods in cell biology and molecular biology form the framework on which this proposal is built.